A directly inhibitory neuropeptide for gonadotrophin release has, until recently, remained unknown. Last year, a novel neuropeptide was found specifically to inhibit pituitary gonadotrophin release in vitro. This peptide has now been named gonadotrophin inhibitory hormone (GnIH). A gonadotrophin inhibitory system is a novel concept for the environmental control of reproduction in any vertebrate. The overall aim of this application is to provide a thorough characterization of the biological activity of the GnIH peptide system. We propose to establish the site(s), nature and mode of action of this peptide system. With such fundamental information in hand, we can then determine whether this peptide system is an integral component of how the brain transduces environmental cues into signals that affect reproduction as a whole. We recognize that there is great potential from the discovery of this peptide system, but some groundwork needs to be performed upon which to build a research program. A thorough characterization and experimental demonstration that the GnIH system plays a fundamental role in the regulation of reproductive function, both biochemical and behavioral, needs to be mapped out. Specific aims are: 1) Based upon our preliminary immunocytochemistry (ICC) data, we will identify the central locations of synthesis and storage of GnIH peptides, using situ hybridization and ICC. 2) With preliminary data in hand, we will build upon on the effects of GnIH on gonadotrophin release in vivo by identifying its specificity of action, and by using established behavioral assays for its effects. This will be performed via central infusion and subsequent behavioral quantification. 3) The locations of action of the GnIH peptide will be identified using iodinated ligands for receptor autoradiography on neural tissues. Potential sex differences in receptor distribution will also be investigated. Receptor binding characteristics will be quantified using Scatchard analysis. The studies outlined in this application will provide a new level of understanding of the neural basis of reproduction that can then be applied to reproductive research in general.